The proposed studies are designed to clarify the role of the basal ganglia (BG) in the control of normal movement and in the pathophysiology of movement disorders of BG origin, such as dyskinesias (involuntary movements), akinesia and rigidity. The activity of neurons in the BG output nuclei (substantia nigra (SN) and globus pallidus (GP) will be examined. In addition, the presumed modulatory role of the subthalamic nucleus (STN) on these structures will be studied. Also relevant to these issues is the nucleus basalis of Meynert (nbM), which is anatomically continuous with the GP and whose neurons, in fact, are intermingled to some extent with those of the GP. Because of this interdigitation of GP and nbM neurons, it is possible that the widespread cholinergic projections of nbM to all cortical areas, including motor cortex, might represent a non-thalamic projection to cortex of BG influences. We have found that the activity of many nbM neurons is movement-related. Comparison of the neuronal activity in SN, GP, STN and nbM in intact primates and in suitable primate models of human BG disorders should lead to a better understanding of the role of these structures in motor control. Three areas of study are proposed: 1) Normal BG/nbM Activity: To analyze the directional specificity of neuronal activity in GP, STN and nbM, we will examine single neuron activity in these structures during performance on a behavioral paradigm which dissociates the direction of limb movement from the pattern of muscular activity. The effects of microstimulation in GP and STN on task performance and muscle tone will also be studied. 2) Dyskinesia Model: The patterns of neuronal discharge in GP will be examined in the primate model of hemiballismus, a disorder in which involuntary movements result from lesions of the STN. The results should clarify the pathophysiology of hemiballismus and provide a direct measure of the altered BG output in this disorder. 3) Rigidity/Akinesia Model: The activity of BG output neurons (in both GP and SN) will be studied in neuroleptic-induced akinesia and rigidity to determine whether these motor abnormalities are associated with increased or decreased BG output.